Effects of the oxadiazine insecticide indoxacarb, DPX-MP062, on neuronal nicotinic acetylcholine receptors in mammalian neurons

Citation
Xl. Zhao et al., Effects of the oxadiazine insecticide indoxacarb, DPX-MP062, on neuronal nicotinic acetylcholine receptors in mammalian neurons, NEUROTOXICO, 20(4), 1999, pp. 561-570
Citations number
26
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROTOXICOLOGY
ISSN journal
0161813X → ACNP
Volume
20
Issue
4
Year of publication
1999
Pages
561 - 570
Database
ISI
SICI code
0161-813X(199908)20:4<561:EOTOII>2.0.ZU;2-C
Abstract
The effects of the novel oxadiazine insecticide DPX-MP062 and its metabolit e (DCJW) on neuronal nicotinic acetylcholine receptors (AChRs) were investi gated using the whole-cell patch clamp technique in rat embryonic cerebral cortical neurons in primary culture. DPX-MP062, applied at concentrations o f 1 and 10 mu M to the bath, reduced the peak amplitude of ACh-induced, rap idly decaying currents to 46.8 +/- 8.8% (n=9) and 15.7 +/- 5.0% (n=4) of th e control, respectively. The effect was irreversible after washing with dru g-free solution. DCJW at either 1 mu M or 10 mu M had similar actions but t he potency was much less than that of DPX-MP062. The slowly desensitizing c urrents induced by low concentrations of ACh (0.1-10 mu M) were augmented a nd those induced by high concentrations of ACh (100-1000 mu M) were inhibit ed by 10 mu M DPX-MP062 with great acceleration of the current decay in a t ime-dependent manner. These effects were use independent and reversible aft er washing with drug-free solution. In contrast, DCJW at 10 mu M did not sh ow significant effects on peak amplitude and decay phase of the slowly dese nsitizing ACh-induced current in cortical neurons. These results indicate t hat the oxadiazine insecticide DPX-MP062 has potent modulating actions on n euronal nicotinic AChRs. The neuronal nicotinic AChR could be one of the pr imary target sites of the insecticide in mammals. (C)1999 Intox Press, Inc.